Molecular imaging involves the use of noninvasive techniques to demonstrate and assess the extent of abnormal biochemical processes and pathophysiological changes that are the basis of disease. CT and standard MRI cannot provide information on the underlying biochemical and physiological properties of disease processes such as cancer. Quantitative PET/CT using novel tracers is ideally suited to provide a more fundamental understanding of disease biochemistry and assess therapy response as well as providing insights on targeted therapy efficacy and novel tracer development. Whole body correlative anatomic and physiological imaging using selectively developed tracers is a critical ingredient for body PET/CT imaging projects since region-of-interest analysis based on a corresponding CT scan is essential for accurate quantification of tracer pharmacodynamics and pharmacokinetics necessary to provide a meaningful comparison with tissue and serum-based biomarkers of disease. This proposal requests funds for a dedicated research whole-body state-of-the-art PET/CT scanner suitable for conducting dynamic imaging in human clinical trials and research studies using sophisticated scanning protocols and/or novel or short lived PET radiopharmaceuticals. This will allow quantitative imaging biomarker characterization of disease states in a wide range of pathologies in oncology, neurology, vascular and metabolic disease, transplant science, infectious and inflammatory pulmonary diseases, including HIV/AIDS co-infection. Emphasis is placed on imaging biomarker assessment of early response to therapy. A better understanding of the molecular basis and early physiological changes in the diseases presented in the 10 Major Projects are expected to result in advances in individualized patient management by promoting the design of adaptive therapy trials. Project goals include specific measurements of disease physiology and drug-target effects giving the earliest indicator of disease response to drug. Development of quantitative imaging for early disease detection and therapy assessment is becoming critical to future disease management protocols and spare patients weeks or months of toxicity and ineffective treatment. Currently, the capability of performing research PET/CT scans across all scientific and medical discipline areas at the University of Pittsburgh is greatly hampered because no PET/CT scanner is available for use in or near the PET-Cyclotron Facility or at the Presbyterian Hospital complex. Furthermore, all clinical PET/CT scanners are operating at full clinical capacity, with no dedicated time available for research studies. In addition, this scanner will replace one of the HR+ (PET only scanners) soon to be out of support. Thus this instrument becomes critical to the success of the ongoing PET neuroimaging program. It is clear that a state-of-the-art PET/CT research resource is needed by current and future NIH funded investigators at the University of Pittsburgh to achieve their scientific goals in their respective biomedical fields.